Know Cancer

forgot password

A Prospective Randomised Phase III Trial to Evaluate Optimal Treatment Duration of First-line Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Primary Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Phase 3
18 Years
Open (Enrolling)
Genital Diseases, Female, Ovarian Diseases, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms

Thank you

Trial Information

A Prospective Randomised Phase III Trial to Evaluate Optimal Treatment Duration of First-line Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Primary Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Inclusion Criteria:

- Signed written informed consent obtained prior to initiation of any study specific
procedures and treatment as confirmation of the patients awareness and willingness to
comply with the study requirements

- Primary diagnosis is confirmed by specialized pathology review (Germany only)

- Females aged ≥ 18 years

- Histologically confirmed, newly diagnosed

- Epithelial ovarian carcinoma

- Fallopian tube carcinoma

- Primary peritoneal carcinoma AND FIGO stage IIb - IV (all grades and all
histological types)

- Patients should have already undergone surgical debulking, by a surgeon experienced
in the management of ovarian cancer, with the aim of maximal surgical cytoreduction
according to the GCIG Conference Consensus Statement. There must be no planned
surgical debulking prior to disease progression. Patients with stage III and IV
disease in whom initial surgical debulking was not appropriate or possible will still
be eligible providing

- the patient has a histological diagnosis and

- debulking surgery prior to disease progression is not foreseen

- Patients must be able to commence cytotoxic chemotherapy within 8 weeks of
cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if
the investigator decides to start chemotherapy within 4 weeks of surgery.

- ECOG 0-2

- Life expectancy > 3 months

- Adequate bone marrow function (within 14 days prior to randomization)

- ANC ≥ 1.5 x 10^9/L

- PLT ≥ 100 x 10^9/L

- Hb ≥ 9 g/dL (can be post-transfusion)

- Adequate coagulation parameters (within 14 days prior to randomization)

- Patients not receiving anticoagulant medication who have an INR ≤ 1.5 and an
aPTT ≤ 1.5 x ULN

- The use of full-dose oral or par-enteral anticoagulants is permitted as long as
the INR or aPTT is within therapeutic limits (according to institution medical
standard) and the patient has been on a stable dose of anticoagulants for at
least two weeks at the time of randomization.

- Adequate liver function (within 14 days prior to randomization)

- Serum bilirubin ≤ 1.5 x ULN

- Serum transaminases ≤ 2.5 x ULN

- Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24 hour urine must
demonstrate ≤ 1 g of protein in 24 hours

- Adequate postoperative GFR > 40 ml/min (estimates based on the Cockroft-Gault or
Jelliffe formula are sufficient)

Exclusion Criteria:

- Non-epithelial origin of the ovary, the fallopian tube or the peritoneum

- Borderline tumours (tumours of low malignant potential) and FIGO stage Ia - IIa

- Planned intraperitoneal cytotoxic chemotherapy

- Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy,
monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)

- Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of
bevacizumab (allowing for the fact that bevacizumab can be omitted from the first
cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left
between the insertion of any central venous access devices (CVADs) and the onset of
bevacizumab treatment.

- Any planned surgery during the study treatment period plus 4 additional weeks to
allow for bevacizumab clearance

- Uncontrolled hypertension (sustained elevation of BP systolic > 150mmHg and/or
diastolic > 100mmHg despite antihypertensive therapy)

- Any previous radiotherapy to the abdomen or pelvis

- Significant traumatic injury during 4 weeks preceding the potential first dose of

- History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI
of the brain is mandatory (within 4 weeks prior to randomization) in case of
suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to
randomization) in case of suspected spinal cord compression.

- History or evidence upon neurological examination of central nervous system (CNS)
disease, unless adequately treated with standard medical therapy e.g. uncontrolled

- Previous Cerebro-Vascular Accident (CVA), Transient Ischaemic Attack (TIA) or
Sub-Arachnoid Haemorrhage (SAH) within 6 months prior to randomization

- Fertile woman of childbearing potential not willing to use adequate contraception
(oral contraceptives, intrauterine device or barrier method of contraception in
conjunction with spermicidal jelly or surgically sterile) for the study duration and
at least 6 months afterwards

- Pregnant or lactating women

- Treatment with other investigational agents, or participation in another clinical
trial testing a drug within the past 4 weeks before start of therapy concomitantly
with this trial

- Malignancies other than ovarian cancer within 5 years prior to randomization, except
for adequately treated

- carcinoma in situ of the cervix

- and/or basal cell skin cancer

- and/or non-melanomatous skin cancer

- carcinoma in situ of the breast

- and/or early endometrial carcinoma as specified below. Patients may have
received previous adjuvant chemotherapy for other malignancies e.g. breast or
colorectal carcinoma if diagnosed over 5 years ago with no evidence of
subsequent recurrence.

- Patients with synchronous primary endometrial carcinoma, or a past history of primary
endometrial carcinoma, are excluded unless ALL of the following criteria for
describing the endometrial carcinoma are met

- Disease stage FIGO stage ≤ IA (tumour invades less than one half of the

- Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell
products or other recombinant human or humanised antibodies

- Non healing wound, active ulcer or bone fracture. Patients with granulating incisions
healing by secondary intention with no evidence of facial dehiscence or infection are
eligible but require 3 weekly wound examinations

- History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to

- Clinically significant cardiovascular disease, including

- Myocardial infarction or unstable angina within 6 months of randomization

- NYHA ≥ Grade 2 Congestive Heart Failure (CHF)

- Poorly controlled cardiac arrhythmia despite medication (patients with
rate-controlled atrial fibrillation are eligible)

- Grade ≥ 3 peripheral vascular disease (i.e. symptomatic and interfering with
activities of daily living requiring repair or revision)

- Current or recent (within 10 days prior to randomization) chronic use of aspirin >
325 mg/day

- Pre-existing sensory or motor neuropathy ≥ Grade 2

- Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contra-indicates the use of an investigational drug or puts the patient at high risk
for treatment-related complications

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS)

Outcome Time Frame:

every 12 weeks until progression or up to 30 months, thereafter every 6 months

Safety Issue:


Principal Investigator

Jacobus Pfisterer, MD PhD

Investigator Role:

Study Chair

Investigator Affiliation:

AGO Study Group


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

November 2011

Completion Date:

November 2021

Related Keywords:

  • Genital Diseases, Female
  • Ovarian Diseases
  • Ovarian Neoplasms
  • Fallopian Tube Neoplasms
  • Peritoneal Neoplasms
  • Ovarian Carcinoma
  • Bevacizumab
  • Paclitaxel
  • Carboplatin
  • Neoplasms
  • Fallopian Tube Neoplasms
  • Genital Diseases, Female
  • Ovarian Neoplasms
  • Ovarian Diseases
  • Peritoneal Neoplasms